New drug gives hope in fight against leukaemia

An international group of haematology scientists, including leading researchers in Oxford, have secured approval from the US Food and drug Administration (FDA) for a new leukaemia drug that has produced exciting results in clinical trials.

The development of Enasidenib has given hope to people with a form of acute myeloid leukaemia (AML), one of the most common and aggressive blood cancers in adults, which is incurable in most patients.

Up to 15% of adult AML patients have a mutation in the IDH2 gene that produces an abnormal IDH2 enzyme that produces a chemical not normally found in blood cells, called 2-hydroxyglutarate (2-HG). 2-HG stops the bone marrow from producing the mature blood cells that are required for life. Instead, immature leukaemia cells accumulate in the patient’s bone marrow and blood. AML patients need regular blood transfusions, and have very poor immune systems because the bone marrow fails to produce neutrophils and monocytes: cells that are essential for fighting life-threatening infections.

Until now, most treatments for AML have involved aggressive chemotherapy drugs, which work by killing AML cells. But these drugs have serious side-effects and are not suitable for the majority of AML patients.

A new drug, Enasidenib, targets the mutated IDH2 enzyme and suppresses production of 2-HG, and may now offer new hope for AML patients. The team of researchers, including clinician scientists in Oxford have published exciting results of the Phase 1 clinical trial of Enasidenib in the medical journal Blood.

The team includes Prof Paresh Vyas (left), the NIHR Oxford BRC’s Co-Theme Lead for Haematology and Stem Cells and Interim Theme Lead for Molecular Diagnostics; and Clinical Haematologist and clinician scientist, Dr Lynn Quek. Both Prof Vyas and Dr Quek are University of Oxford academics, and Oxford University Hospitals consultants who work in the Myeloid Service at the Churchill Hospital.

In the clinical trial, Enasidenib was effective in 40% of the 176 AML patients who have the IDH2 mutation, including 19% who achieve complete remission.

Patients – most of whom had few side-effects to the drug – had improved immune systems and required fewer – or no – blood transfusions.

Crucially, given that most patients in this trial had not responded to other types of treatment for AML, Enasidenib represents an important addition to the currently limited range of effective treatments for this disease.

Enasidenib works in a completely different way to conventional chemotherapy drugs: instead of killing leukaemia cells, it re-programmes them to mature into neutrophils and monocytes that can then function normally as part of a healthier immune system.

This promising clinical data, together with supporting scientific data that show how Enasidenib works in patients, secured FDA approval for Enasidenib earlier this month.

Enasidenib is not effective for all patients, but research findings suggest that this could be due to the presence of other gene mutations.

The Oxford team are leading an ongoing research programme to find out how resistance to Enasidenib can be overcome, and if Enasidenib can work more effectively in combination with other AML therapies.